Apoptosis, a form of genetically programmed cell death, occurs at a high rate throughout life in many human tissues. The resulting cell corpses are typically engulfed by other cells and degraded in the lysosome. However, recent research has revealed that there are other routes for elimination of apoptotic corpses as well and that defects in these alternative cell clearance mechanisms may be linked to human diseases, including cancer. The overall goal of this study is to characterize a novel mechanism of cell clearance in the planarian flatworm, Schmidtea mediterranea. Preliminary data suggest that apoptotic cells in planarians are engulfed by phagocytic cells, just as they would be in the canonical cell clearance mechanism, but subsequently emptied into the digestive system for excretion instead of being degraded. This hypothesis will be addressed in two specific aims. First, electron microscopy will be used to visualize key steps in the cell clearance process in vivo, while the roles of candidate genes predicted to play a role in engulfment will be evaluated by RNAi and in situ hybridization. Second, RNA-Seq will be utilized to identify novel genes involved in apoptotic cell clearance. These genes will also be characterized by RNAi and in situ hybridization. Because planarians share key characteristics with humans, including the utilization of an evolutionarily conserved mechanism of apoptosis, this work is likely to be relevant to our understanding of human health and disease. This project will also offer undergraduate students at Keene State College an opportunity to engage in discovery-based research.